The major objective of the proposed research is to elucidate the mechanism of the immunological impairment of the myeloma bearing host by isolating and characterizing the immunosuppressive soluble factors and by identifying the suppressive cell (B or T cell, macrophage or other). In order to achieve these goals, we will: 1) continue to study the suppressive activity of serum or ascites from tumor-bearing mice (initially TEPC-183 (IgMk)) and/or of cell extracts of appropriate tissues; 2) identify the suppressor cell by in vivo transfer experiments and by in vitro co-culturing experiments; 3) isolate and characterize the suppressive factor; 4) compare properties of this factor(s) with immunosuppressive substances described in other laboratories. The effect of suppressive cells and/or factors on the immune response will be studied at the cellular and molecular level by using chemically defined "T" dependent antigens (2,4-dinitrophenyl (DNP)) and "T" independent clinically relevant antigens; such as pneumococcal polysaccharides type III (SSS-III). The effect of factors on the in vivo and in vitro immune response will be determined by the PFC and RFC tests. The antibody response for DNP and for SSS-III will be quantitated using the highly sensitive radioimmunoassay, which detects 1-10 micron g of Ab N/ml of serum. In addition, the effect of the tumor and of suppressive factors in reucing the protection of immunogenic doses of SSS-III against challenge by virulent pneumococci will be investigated. The in vivo and in vitro effect of stimulation by B and T cell mitogens (PHA, ConA, PWM and LPS) on lifting the immunosuppression and the effect of chemotherapeutic agents which are themselves immmunosuppressive will also be investigated.